Preparation of acetoacetyl aromatic acid amides



Patented Apr. 4, 1939 4 UNITED STATES PATENT OFFICE 2,152,180 rnaraaa'rionor acc'roaccmaaomno aom AMIDES Albert B. Boese, 1'... Pittsburgh, Pa., assignor to Carbide and Carbon Chemicals Corporation, a corporatiomof New York No Drawing. Application July '9, 1936,

- Serial means .14 Claims. (CL 260-582) boiling inert solvent in which the acetoacetyl aro'matic amide is quite soluble when hot, such as acetone, dioxan, benzene and toluene.

The production of acetoacetanilide by reacting aniline and diketene already is known; and the process therefor is covered in'U. S. Patent 1,982,- 675 issued December 4, 1934, to George H. Law.

It has now been discovered that by reacting diketene with the higherv primary aromatic monoamines, primary aromatic poly-amines, and with substituted primary aromatic monoand polyamines, under conditions where the speed and violence of thereaction and the temperature of the reaction mixture is at all times under control,

it is readily possible to produce acetoacetic acid amides from such amines and substituted amines I in very satisfactory yields.

According to the invention, diketene and such a primary aromatic amine 'or substituted amine are slowly reacted in the presence of a solvent for the reactants which is inert with respect to each, and in which thetresultant amide is soluble.

Preferably the diketene is introduced slowly into 3 an agitated solution of the amine in the inert solvent, at an elevated temperature which is desirably around the boiling point or refluxing point thereof. After completion of the reaction, the

solvent is removed by distillation, and the acetoacetic acid amide is separated from any unreacted amine and recovered. Thus, notwithstanding the powerful polymerization tendency of diketene, and the high chemical reactivity of primary monoand poly-amines and substituted 4 amines, including those derived from aromatic hydrocarbons containing in their molecules two or 'more, interconnected benzene nuclei, either condensed or uncondcnsedJt is possible,-'-by utilizing the presentinventiom-tb prepare from these compoundsvaluable acetoacetyl aromatic amides with good yields and efliciencies.

Bis-para-amine derivatives of diphenyl and its homologues', amino diphenylmethana; a and p t naphthylamines and their homologues, and ar alkyl amines such as benzylamine and its homologues, exemplify aromaticamines which react with diketene to yield these acetoacetyl amides. The following examples serve to illustrate the so invention:

, Eirmru 1 7 Preparation of bis-acetoacetyl orthotolidine A solution of 212 grams (1 mol) of orthotolidine in 2100 cc. of acetone was heated under reflux to 5 the boiling point of acetone, and 1'76 grams (1.05 mol) of diketene was slowly added over a period of 15 minutes while constantly stirring the mixture. After approximately an hour the reaction product began to separate. Refluxing was 10 continued for 3 hours and thereaction mixture,

a free-flowing crystalline slush. was then allowed to stand overnight, and the crystallized product was separated by filtration. There thus wasobtained 245 grams of bis-acetoacetyl orthotolidlne '15 which melted at 203 to 204 C. The filtrate was concentrated to half its original volume by distillation; cooled, and a further 29 grams of the bis-acetoacetyl orthotolidine, melting point 202 to 203 0., was obtained. On further concentration, an additional 63 .grams of bis-acetoacetyl orthotolidine, melting point 201 to 202 C., was obtained which was separated by filtration and washed with acetone.

Thus a yield of diacetoacetyl tolidine of 88.7% was secured, based upon the orthotolidine, with 25 a diketene efliciency of 84.9% based upon diacetoacetyl tolidine. Acetone was removed by distillation from the mother liquor from the final filtration and the residue treated with 200 cc. of a 5% aqueous sodium hydroxide solution. The caustic alkali-insoluble material, consisting chiefly of diacetyl orthotolidine, was separated by filtration. The filtrate was then acidified with 25 cc. of concentrated hydrochloric acid, and the I precipitated diacetoacetyl orthotolidine separated 35 on a filter, washed, and air dried. There was obtained an additional 8 grams of somewhat impure diacetoacetyl orthotolidine which melted at to 200 0,, increasing the total yield to 90.8%.

As acidifying agents, otheracids, such as sulfuric or acetic, may be used. I

The reaction involved is indicated by the equaflog W HTNQQNHri-zcmcOcH c-o --t 45 Hr I Ht v (o-Tolidlno) (Dihctsnc) OHICOOHIO oNnQQrmooomooom El I HI Diccetclcctylo-tclidine Benzene, toluene and other aromatic hydrocorg EXAMPLE 2 Preparation of bis-acetoacetyl benzidine To a solution of 36.8 grams of benzidine (bisparadiamino-diphenyl) in 400 cc. of acetone was added slowly 35.3 grams ofdiketene. The solution then was heated under reflux with agitation for 4 hours, during which time a crystalline reaction product, diacetoacetyl benzidine, separated out. The mixture was cooled to room temperature and filtered. Thus there was obtained 57 grams of pure diacetoacetyl benzidine which melted with decomposition at 233 C. The acetone' extract was evaporated, and yielded 10.6

grams of a caustic alkali-insoluble material. The residue was suspended in100 cc. of warm acetone, and the resulting suspension filtered while warm. There was obtained 4.6 grams of acetone-insoluble diacetyl benzidine, melting at from 325 to 330 C. Concentration of the acetone filtrate yielded 4.2 grams of monoacetyl benzidine, melting at from 193 to 195 C. The percentage conversion of the benzidine was 80%; and the yield of the bis-acetoacetyl benzidine on the basis of the amount of benzidine that reacted was 97.5%.

I EXAMPLE 3 Production of acetoacet-alpha-naphthylamide To a cold .solution of 8.4 grams of diketene in cc. of dioxan was added in the cold a solution of 14.3 grams of alpha-naphthylamine in 50 cc. of dioxan. After .24 hours the odor of diketene had disappeared, and a portion of the reaction product had crystallized from the solution. Addition of petroleum ether caused a further; precipitation. The crystallized reaction product was separated by filtration of the mixture, washed with petroleum ether, and then was and-recovered: 5"

recrystallized from benzene. A yield of over was obtained of the acetoacet-alphanaphthylamide in the form 01 almost colorless needles which melted at 118 to C.

By introducing diketene to a refluxing solution of the" alpha-naphthylamine in dioxan, the reaction may be completed in a shortertime.

The equation for the reaction maybe written as follows;

NH: 7 omooomcomz omooon= =o Alpha m n- (Dike time) (Acetoacetthylamine j alpha-naphthylsmide) C Exunrn4 Under, conditions" substantially identical with those recited inExamP eB, s r but usin betanaphthy-lamine instead of alpha-naphthylamine,-'

a yield of over 99% or aceto-acet-beta-naphthyl- Q melt ng a .ijq w s produced.

mac w.

The acetoacetyl aromatic acid invention are in general used in the dyestufl industry as intermediates for the production of dyes of the Hansa yellow type. They also, under ring closure in the presence of dehydrating agents, form hydroxymethyl quinoline derivatives. Di-

aceto-acetyl tolidine, known as Naphthol As-G,

is a commercially important dyestufi component.

The following examples illustrate the production of substituted acetoacetanflides in accordance with the invention;

EXAMPLE 5 Para-hydromy acetoacetanilide To a refluxing solution of 10.9 grams of paraamino-phenol in cc. ofacetone 8.4 grams of After refluxing diketene was added dropwise. the mixture for one hour, the acetone was removed by distillation, leaving 19 grams of viscous residue which slowly crystallized upon cooling.

This product was purified by recrystallization from water after treatment of the water solution with decolorizing carbon. The reaction product, para-hydroxy acetoacetanilide, was recovered in the form of colorless needles which melted at between 88 and 90 C. This product is soluble-in alcohols, ketones, esters and water, but only slightly soluble in others, chlorinated solvents,;

and aromatic and aliphatic hydrocarbons. It has the apparent structure designated by the formula noONnoo omcocn.

Para-hydroxy aoetoacetanilide formed by the reaction of one mole of diketene with one of the amine.

EXAMPLE 6 Para-nitroacetoacetdnilide To a refluxing solution of 50 grams of paranitroaniline in 600 cc. of acetone 33.4 grams of diketene were added dropwise. After refluxing.

the solution for 4 hours, the acetone was distilled ad, and the resultant crystalline residue was treated with a dilute solution of. the theoretical amount of sodium hydroxide for dissolving the resultant amide. The unreacted para-nitroaniline then was separated by filtration. The flltrate was neutralized with. dilute hydrochloric acid, whereupon para-nitroacetoacetanilide precipitated. This was flltered'oif, washed with water, and air-dried, giving a yield of 65% thereof. When recrystallized .from water it occurred as a pale yellow crystalline compound which melted at 124 tol24'.5 C. It has the apparent structure indicated by the formula rnzoocmooom NO: Pam-nltroaeetoacetenilide and is formed by the reaction of equimolecular proportions of the reactants.

Exunu 7 Pdro-ethoxy acetoacetanilide To a refluxing solution of 34 grams of paraphenetidine in 250 cc.- of, acetone was added slowly 21 grams of diketene. The heat developed by the resmtant'reaction was suilicient to keep capo-O-mrcoomcocn Pam-ethoxy acetoae'etanilide and results-from the interaction of euuimolecular proportions of the reactants.

Exam? 8 Ortho-methvzil acetoacetanilide Following the procedure described in Example 1 and using 31 grams of ortho-anisidine and 21 grams of diketene there were obtained 45 grams oi ortho-methoxy acetoacetanilide in the form of colorless platelets, which melt at between and 86 0., corresponding to a yield of around 87%. The compound has the apparent structure NHCOOHaCO-CHa To" a refluxing solution oi 27 grams oi metaphenylene diamine in 250 cc. of acetone 4'7 grams of diketene were added dropwise. Thereafter the acetone solution was concentrated and cooled, whereupon an almost quantitative yield of diacetoacetyl ineta-phenylene diamine crystallized out and was filtered oil and air-dried. Upon recrystallization from glacial acetic acid, it occurred as a" colorless crystalline compound that melted at between 107- and 108 C. and was soluble in water, alcohols, ketones, esters, and ethers, but was practically nated solvents and in aromatic and aliphatic hydrocarbons. It has the apparent structure NHOOCHJCO CH Nncoomcoon. DIIcetomtYLmcta-phmylene diaminc Exmu 10 Diacetoacetyl pam-phenyle ne diamine When addition of the This prodinsoluble in chloriline compound which melts at between-176 and 178 C. and has the apparent structure nncoomcocm nnoocnlcooni v Diaeettac etyl para-phenylene diamine It will .be understood that the method of the present invention is not limited to the production of the particular acetoacetyl aromatic amides specifically recited in the specification. On the contrary, the method may be utilized for the production oi acetoacetyl amides from other aro-' matic primary monoand poly-amines of simple and condensed aromatic hydrocarbons, and from other substituted aromatic monoand polyamines.

By the expression is intended to designate those primary amines having more than 6 carbon atoms in their molecules.

The invention is susceptible of modification within the scope of the appended claims.

I claim: i

1. Method of preparing an acetoacetyl aromatic acid amide, which comprises reacting 'diketene and a primary amine selected from the group consisting of the aromatic mono amines having more than six carbon atoms in their mole- Y cules, the aromatic poly amines, and the substituted aromatic mono and poly amines, in the presence of a solvent inert to the reactants, separating fromv the reaction mixture the solid prod? ucts thus formed, removing therefrom excess reactants, and recovering the resultant acetoacetyl amide.

2.-Method of preparing an acetoacetyl aromatic acid amide, which comprises refluxing diketene and a primary amine selected-from the group consisting of the aromatic mono amines having more than six carbon atoms in their molecules, the aromatic poly amines, and the substituted aromatic mono and polyamines, in the presence of a solvent inert to the reactants, separating from the reaction mixture the solid products thus formed, removing therefrom excess reactants, and recovering the resultant acetoacetyl amide.

3. Method as defined in claim 1, wherein acetone is employed as the said solvent.

4. Method of preparing bis-acetoacetyl o-tolihigher aromatic mono amines appearinggin the accompanying claims dine, which comprises heating and reacting dikeacetanilide, which comprises reacting diketene and a compound selected from aniline derivatives in which there is atom of the benzene ring a radical selected irom the group consisting of hydroxyl, nitro, amino and alkoxy radicals. in the presence of a solvent inert to the reactants, and recovering from the directly attached to a'carbon resultant reaction mixture the substituted acetoacetanilide thus produced.

7. Method for preparing a hydroxy acetoacetanilide, which comprises heating and reacting diketene and a primary amino phenol in the presence of a volatile solvent for the reactants which is inert thereto, and recovering from the resultantreaction mixture the hydroxy acetoacetanilide thus produced.

8. As a chemical compound, para-hydroxyacetoacetanilide, being a solid melting at between 88- and 90 C., and being soluble in alcohols, ketones, esters and water, and only slightly soluble in ethers and chlorinated solvents.

9. Method-for producing an acetoacetyl arcmatic amide, which comprises reacting diketene and a primary amine selected from the group consisting of the aromatic monoamines having more than six carbon atoms in their molecules,

the aromatic polyamines, and the substituted aromatic amines in which there is directly attached to at least one carbon atom of a benzene ring a radical selected from the group consisting of hydroxyl, m'tro, and alkoxy radicals, in the presence of a solvent-inert to the reactants, and

recovering from the resultant reactionmixture 7 the acetoacetyl aromatic amide thus produced,

10. Method for preparing an acetoacetyl aromatic amide, which comprises reacting diketene and a para primary diamino derivative ofan-aromatic hydrocarbon having two benezene nuclei directly united in its molecule, in the presence 01' an inert Solvent for the reactants, and thereafter recovering from the'resultant reaction mixture the acetoacetyl aromatic amide thus produced.

11. Methodfor preparing an acetoacetyl aromatic amide, which comprises reacting diketene and a para primary diamino diphenyl, in the presence of an inert solvent for the reactants,'

I 13. Method forpreparing para -hydroxy acetoacetanilide, which comprises heating'and reacting diketene and para amino phenol in the presence of a volatile solvent for the reactants which is inert thereto, and recovering from the resultant reaction mixture the para-hydroxy acetoacetanilide thus produced.

14. Method for producing anacetoacetyl aromatic amide, which comprises slowly introducing diketene in small successive portions into an agitated solution in an inert volatile solvent of a primary amine selected from the group consisting of the aromatic monoamineshaving more than six carbon atoms in their molecules, the aromatic poly amines, andthe substituted aromatic amines in whichthere is directly attached a to at least one carbon atom of a benzene ring a radical selected from the group consisting of hydroxyL'nitro, and alkoxy radicals, and recovering from the resultant reaction mixture the acetoacetyl aromatic amide thus produced. I

- ALBERT B. BOESE, JR. 

